Clinical Briefs

With Comments from John La Puma, MD, FACP

Alpha-Tocopherol and Selegiline in the Treatment of Alzheimer's Disease

June 1998; Volume 1: 71

Source: Sano M, et al. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. N Engl J Med 1997;336:1216-1222.

To determine whether selegi- line, alpha-tocopherol (vitamin E), or both would slow the clinical deterioration associated with moderately severe Alzheimer's disease, Sano et al. conducted a double-blind, placebo-controlled, randomized trial in 23 university centers.

A total of 341 patients without other central nervous system (CNS) diseases or use of psychoactive medication received selegiline (5 mg bid), dl-alpha-tocopherol (1000 IU bid), both, or placebo. Outcomes, adverse events, and drug or metabolite levels were assessed at one month and then quarterly for two years.

There was no difference in time to death, institutionalization, severe dementia, or loss of the ability to perform two of three activities of daily living. These outcomes were significantly delayed by selegiline (mean survival, 655 days), alpha-tocopherol (670 days), and combination therapy (585 days). There were also significant improvements in function and behavior in adjusted analyses.

In patients with moderately severe Alzheimer's, treatment with either selegiline or alpha-tocopherol slows the progression of disease.

Comment

This is a carefully done, NIH-supported trial by members of the Alzheimer's Disease Cooperative Study.

Selegiline is an MAO inhibitor, and the authors speculate that it may act as an antioxidant; it has prolonged the time during which Parkinson's patients function well enough to work. It also increases catecholamines. Alpha-tocopherol is also an anti-oxidant that has been shown, in lower doses, to reduce the risk of coronary artery disease. Alpha-tocopherol has not been of benefit in studies of patients with Parkinson's or Huntington's diseases.

Selegiline and alpha-tocopherol, both individually and together, reduced the frequency of death, institutionalization, severe dementia, or loss of the ability to perform two of three activities of daily living. Combined treatment was not significantly more effective than either treatment individually. Alpha-tocopherol significantly delayed institutionalization; selegiline did not. No other individual treatment/end point outcomes were observed.

The rate of falls and of syncope was significantly increased in both treatment groups over placebo, and especially increased in the combined treatment group. These events did not lead to discontinuation of treatment.

Recommendation

High-dose vitamin E seems to be as safe and effective as selegiline in patients with Alzheimer's disease. Combining the two, however, is not recommended, as falls and syncope were most prevalent in the combined treatment group.


Vitamin E and Immune Response in Elderly Subjects

June 1998; Volume 1: 71-72

Source: Meydani SM, et al. Vitamin E supplementation and in vivo immune response in healthy elderly subjects: A randomized controlled trial. J Am Med Assoc 1997;277:1380-1386.

To determine whether long-term supplementation with vitamin E enhances in vivo, clinically relevant measures of cell-mediated immunity in healthy elderly subjects, the authors performed a randomized, double-blind, placebo-controlled intervention with 88 free-living subjects, 65 years and older. Assigned to a placebo group or to groups consuming 60, 200, or 800 mg daily of dl-alpha-tocopherol (vitamin E), subjects were followed for 235 days.

Primary outcomes were antibody responses to delayed type hypersensitivity skin response (DTH); hepatitis B, tetanus, diphtheria, and pneumococcal vaccines; and autoantibodies to DNA and thyroglobulin. All were assessed before and after supplementation.

Subjects receiving 200 mg/d had a 65% increase in DTH and a six-fold increase in antibody titer to hepatitis B compared with placebo (17% and three-fold, respectively) and a significant increase in antibody titer to tetanus vaccine. Subjects receiving 60 mg/d had a 41% increase in DTH and a three-fold increase in antibody titer to hepatitis B compared with placebo. The 800 mg/d group had a 49% increase in DTH and a two-and-a-half-fold increase in antibody titer to hepatitis B.

Vitamin E supplementation had no effect on antibody titer to diphtheria and did not affect immunoglobulin levels or levels of T and B cells, or autoantibody levels. No adverse effects were observed with supplementation.

Our results indicate that a level of vitamin E greater than currently recommended enhances certain clinically relevant in vivo indices of T-cell-mediated function in healthy persons.

Comment

A lower immune response predicts higher morbidity and mortality in the elderly. Even so, it's often hard to know what to make of "increases immune function" claims. This is a carefully done study that puts substance behind its assessment.

Pill counts and vitamin levels were used to check adherence; there was no difference between average age, BMI, gender, or race between placebo and intervention groups. Induration index, IgG antibody levels against pneumococcal vaccine, and antibody titer against hepatitis B were measured. Autoantibody levels against DNA and thyroglobulin were also measured because "it has been suggested that stimulation of immune function in the aged might also result in the undesirable effect of increased autoantibody function."

The middle dose of vitamin E gave the best immunologic response, suggesting a threshold effect. When all vitamin E groups were combined, the incidence of self-reported infections was 30% lower than placebo (P = 0.10).

Recommendation

I would suggest 200 mg of vitamin E daily to your elderly patients who want to help prevent these infections. Vitamin E is best taken as a supplement (unless your patients will keep off the weight that they'll put on eating 1.2 pounds of almonds or hazelnuts daily).


Antioxidants and Memory Performance in the Elderly

June 1998; Volume 1: 72

Source: Perrig WJ, et al. The relation between antioxidants and memory performance in the old and very old. J American Geriatr Soc 1997;45:718-724.

To investigate whether plasma levels of alpha-tocopherol (vitamin E), ascorbic acid (vitamin C), and beta carotene (vitamin A) correlate with memory performance in older adults, Pern et al used longitudinal and cross-sectional comparisons to study 442 randomly selected healthy subjects ages 65-94 years (mean, 75; 312 male; 132 female) in the city of Basle, Switzerland, in 1993. The same vitamin parameters had been measured previously in 1971 in the same sample. Memory variables were priming, working-memory, free recall, recognition, and the WAIS-R vocabulary test (semantic memory).

Correlations showed significant stability of the plasma antioxidants over the time lag of 22 years (alpha tocopherol: R = 0.47, P < 0.001; beta carotene: R = 0.43, P < 0.001; ascorbic acid: R = 0.22; P < 0.001). Free recall, recognition, and vocabulary, but not priming and working memory, correlated significantly with ascorbic acid and beta carotene in the cross-sectional 1993 data as well as in the longitudinal analysis. These two antioxidants remained significant predictors, especially of semantic memory, after controlling for age, education, and gender using multiple regression analyses and analyses of variances (ANOVAs).

Among people ages 65 and older, higher ascorbic acid and beta carotene plasma levels are associated with better memory performance. Vitamin E levels and memory function were not correlated.

Comment

Food and medicine are drawing closer than ever, now that good science is illuminating what good eaters have known for a long time: A diet that is plant-based is healthful. A diet rich in fruits and vegetables and their antioxidants also appears to deter common forms of memory loss in old age.

This is a well-done prospective epidemiologic study using free-living subjects in Switzerland (where the memory of free chocolate for air travelers passing through Zurich remains too distant).

Because vitamin levels were stable over time, and because only 6% of the studied cohort mentioned vitamin supplementation, the authors believe that their population's food preferences were responsible for their vitamin levels. The supplementation subgroup did not have higher levels of plasma vitamins or better memory scores.

Beta carotene (a precursor of vitamin A) and vitamin C levels predicted better memory, especially semantic memory, in elderly subjects. Plasma beta carotene and ascorbic acid levels reflect recent intake and an emphasis on the consumption of fruits and vegetables. Good food sources include sweet potatoes (14.9 mg beta carotene in one medium potato), kiwis (98 mg vitamin C in 3.5 ounces), and kale (5.3 mg beta carotene and 120 mg vitamin C in 3.5 ounces). The deeper the color, generally, the greater the beta carotene and vitamin C content.

To maximize flavor, roast sweet potatoes in the oven at 425 degrees until soft and gooey. Eat kiwis whole, or blend six with two cups of strawberries, two ripe bananas, and three cups of ice. Slice a bunch of kale ribbon thin, and stir fry with a large white onion, minced garlic, and rings of red pepper, topped with a squeeze of lemon and a squirt of soy sauce. Delicious!

Recommendation

Evidence-based medicine suggests that patients ages 65 and older with higher beta carotene and ascorbic acid levels do better on tests of memory. Patients should eat at least five orange and red fresh vegetables and dark leafy greens daily to deter memory loss.